These studies are designed to demonstrate a new role for wild type Kras2 in lung carcinogenesis following inhalation exposure of heterozygous Kras2 deficient mice. 1,3-Butadiene was selected as the test agent because preliminary data demonstrated that in lung neoplasms from mice exposed to 1,3-butadiene, the signature Kras codon 13 CGC mutation is consistently present and many of the tumors with this mutation also have loss of the wild type allele. The proposed studies will investigate the hypothesis that loss of the wild type ras allele following 1,3-butadiene exposure will accelerate tumorigenesis mediated by the oncogenic ras allele. Current efforts are directed at obtaining and breeding the A/Jx129 and Sv-Kras2+/- mice. These animals will be bred and maintained at the Ohio State University Comprehensive Cancer Center, and delivered to the NIEHS inhalation facility 2-weeks prior to the start of the study. The 1,3-butadiene has been procured and chemical analyses are being conducted on the bulk chemical. The exposure room is being reconfigured and the generation and monitoring systems developed.